College of Life and Environmental Sciences, Shanghai Normal University, No. 100 Guilin Road, Shanghai 200234, China.
Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai 200241, China.
Acta Biomater. 2018 Apr 1;70:140-153. doi: 10.1016/j.actbio.2018.02.010. Epub 2018 Feb 15.
A chronic wound in diabetic patients is usually characterized by poor angiogenesis and delayed wound closure. The exploration of efficient strategy to significantly improve angiogenesis in the diabetic wound bed and thereby accelerate wound healing is still a significant challenge. Herein, we reported a kind of aligned porous poly (l-lactic acid) (PlLA) electrospun fibrous membranes containing dimethyloxalylglycine (DMOG)-loaded mesoporous silica nanoparticles (DS) for diabetic wound healing. The PlLA electrospun fibers aligned in a single direction and there were ellipse-shaped nano-pores in situ generated onto the surface of fibers, while the DS were well distributed in the fibers and the DMOG as well as Si ion could be controlled released from the nanopores on the fibers. The in vitro results revealed that the aligned porous composite membranes (DS-PL) could stimulate the proliferation, migration and angiogenesis-related gene expression of human umbilical vein endothelial cells (HUVECs) compared with the pure PlLA membranes. The in vivo study further demonstrated that the prepared DS-PL membranes significantly improved neo-vascularization, re-epithelialization and collagen formation as well as inhibited inflammatory reaction in the diabetic wound bed, which eventually stimulated the healing of the diabetic wound. Collectively, these results suggest that the combination of hierarchical structures (nanopores on the aligned fibers) with the controllable released DMOG drugs as well as Si ions from the membranes, which could create a synergetic effect on the rapid stimulation of angiogenesis in the diabetic wound bed, is a potential novel therapeutic strategy for highly efficient diabetic wound healing.
A chronic wound in diabetic patients is usually characterized by the poor angiogenesis and the delayed wound closure. The main innovation of this study is to design a new kind of skin tissue engineered scaffold, aligned porous poly (l-lactic acid) (PlLA) electrospun membranes containing dimethyloxalylglycine (DMOG)-loaded mesoporous silica nanoparticles (DS), which could significantly improve angiogenesis in the diabetic wound bed and thereby accelerate diabetic wound healing. The results revealed that the electrospun fibers with ellipse-shaped nano-pores on the surface were aligned in a single direction, while there were DS particles distributed in the fibers and the DMOG as well as Si ions could be controllably released from the nanopores on the fibers. The in vitro studies demonstrated that the hierarchical nanostructures (nanopores on the aligned fibers) and the controllable released chemical active agents (DMOG drugs and Si ions) from the DS-PL membranes could exert a synergistic effect on inducing the endothelial cell proliferation, migration and differentiation. Above all, the scaffolds distinctly induced the angiogenesis, collagen deposition and re-epithelialization as well as inhibited inflammation reaction in the wound sites, which eventually stimulated the healing of diabetic wounds in vivo. The significance of the current study is that the combination of the hierarchical aligned porous nanofibrous structure with DMOG-loaded MSNs incorporated in electrospun fibers may suggest a high-efficiency strategy for chronic wound healing.
糖尿病患者的慢性创面通常表现为血管生成不良和愈合延迟。探索有效策略以显著改善糖尿病创面床中的血管生成，从而加速创面愈合仍然是一个重大挑战。在此，我们报道了一种含有载二甲氧羰基甘氨酸（DMOG）的介孔硅纳米粒子（DS）的定向多孔聚（L-丙交酯）（PLA）电纺纤维膜，用于糖尿病创面愈合。PLA 电纺纤维沿单方向排列，纤维表面原位生成椭圆形纳米孔，而 DS 均匀分布在纤维中，纳米孔可控制释放纤维上的 DMOG 和 Si 离子。体外结果表明，与纯 PLA 膜相比，定向多孔复合膜（DS-PL）可刺激人脐静脉内皮细胞（HUVEC）的增殖、迁移和血管生成相关基因表达。体内研究进一步表明，所制备的 DS-PL 膜可显著改善糖尿病创面床中的新生血管、再上皮化和胶原形成，并抑制炎症反应，从而刺激糖尿病创面愈合。总之，这些结果表明，具有层次结构（纤维上的纳米孔）和从膜中可控释放 DMOG 药物以及 Si 离子的组合，可对糖尿病创面床中血管生成的快速刺激产生协同作用，为高效糖尿病创面愈合提供了一种潜在的新型治疗策略。
